| Autor: |
Aitken-Buck HM; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand., Babakr AA; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand., Fomison-Nurse IC; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand., van Hout I; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand., Davis PJ; Department of Cardiothoracic Surgery, Dunedin School of Medicine, Dunedin Hospital, Dunedin, New Zealand., Bunton RW; Department of Cardiothoracic Surgery, Dunedin School of Medicine, Dunedin Hospital, Dunedin, New Zealand., Williams MJA; Department of Medicine and HeartOtago, Dunedin School of Medicine, Dunedin Hospital, Dunedin, New Zealand., Coffey S; Department of Medicine and HeartOtago, Dunedin School of Medicine, Dunedin Hospital, Dunedin, New Zealand., Jones PP; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand., Lamberts RR; Department of Physiology and HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. |
| Abstrakt: |
The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the proarrhythmic effect of EAT. EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-h EAT culture media ( n = 8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Coculture with β-adrenergic agonists isoproterenol ( n = 4) and BRL37344 ( n = 13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae ( n = 10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula-developed force (maximal 2.9-fold increase, P < 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P = 0.002) and relaxation (1.8-fold increase, P = 0.007). Additionally, the postrest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca 2+ handling. EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behavior in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect. |
